Dairy fat intake is associated with glucose tolerance, hepatic and systemic insulin sensitivity, and liver fat but not β-cell function in humans

Abstract

Background: Plasma phospholipid concentrations of trans-palmitoleic acid (trans-16:1n-7), a biomarker of dairy fat intake, are inversely associated with incident type 2 diabetes in 2 US cohorts.

Objective: The objective was to investigate whether the intake of trans-16:1n-7 in particular, or dairy fat in general, is associated with glucose tolerance and key factors determining glucose tolerance.

Design: A cross-sectional investigation was undertaken in 17 men and women with nonalcoholic fatty liver disease and 15 body mass index (BMI)- and age-matched controls. The concentrations of trans-16:1n-7 and 2 other biomarkers of dairy fat intake, 15:0 and 17:0, were measured in plasma phospholipids and free fatty acids (FFAs). Liver fat was estimated by computed tomography-derived liver-spleen ratio. Intravenous-glucose-tolerance tests and oral-glucose-tolerance test (OGTT) and hyperinsulinemic-euglycemic clamps were performed to assess β-cell function and hepatic and systemic insulin sensitivity.

Results: In multivariate analyses adjusted for age, sex, and BMI, phospholipid 17:0, phospholipid trans-16:1n-7, FFA 15:0, and FFA 17:0 were inversely associated with fasting plasma glucose, the area under the curve for glucose during an OGTT, and liver fat. Phospholipid trans-16:1n-7 was also positively associated with hepatic and systemic insulin sensitivity. None of the biomarkers were associated with β-cell function. The associations between dairy fat intake and glucose tolerance were attenuated by adjusting for insulin sensitivity or liver fat, but strengthened by adjusting for β-cell function.

Conclusion: Although we cannot rule out reverse causation, these data support the hypothesis that dairy fat improves glucose tolerance, possibly through a mechanism involving improved hepatic and systemic insulin sensitivity and reduced liver fat.

Trial registration: ClinicalTrials.gov NCT01289639.

© 2014 American Society for Nutrition.

Figures

FIGURE 1.

Bivariate associations in subjects with nonalcoholic fatty liver disease (▴) and controls (•) between biomarkers of dairy fat intake and fasting glucose concentrations (A; r = −0.530, P = 0.002; n = 32); glucose tolerance (B), as assessed by the total AUC for glucose during a 2-h frequently sampled oral-glucose-tolerance test (r = −0.516, P = 0.004; n = 30); liver fat content (C), as assessed by the liver-spleen ratio in a computed tomography scan (liver-spleen ratio is inversely associated with liver fat mass: r = 0.488, P = 0.005; n = 32); and hepatic insulin resistance (D), as assessed by the basal hepatic glucose production rate (mg/min) × fasting insulin concentration (pmol/L) (r = −0.497, P = 0.007; n = 28).

FIGURE 2.

The mechanism through which higher intakes of dairy fat in general, or trans-palmitoleic acid in particular, may affect fasting glucose concentrations and glucose tolerance include a reduced liver fat content leading to improved hepatic and systemic insulin sensitivity.